A novel strategy for the chiral 2,4,5-triol moiety and its application to the synthesis of seimatopolide A and (2S,3R,5S)-(-)-2,3-dihydroxytetradecan-5- olide

Article abstract of DOI:10.1016/j.tetlet.2012.08.027

A highly stereoselective approach to the total synthesis of seimatopolide A and (2S,3R,5S)-(-)-2,3-dihydroxytetradecan-5-olide is described via a common polyketide precursor by means of Prins reaction and MacMillan aminoxylation sequence.

Full text of DOI:10.1016/j.tetlet.2012.08.027

Tetrahedron Letters 53 (2012) 5749–5752
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A novel strategy for the chiral 2,4,5-triol moiety and its application
to the synthesis of seimatopolide A and (2S,3R,5S)-(ꢀ)-2,3-
dihydroxytetradecan-5-olide
⇑
B. Phaneendra Reddy, T. Pandurangam, J. S. Yadav, B. V. Subba Reddy
Natural Products Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly stereoselective approach to the total synthesis of seimatopolide A and (2S,3R,5S)-(ꢀ)-2,3-
dihydroxytetradecan-5-olide is described via a common polyketide precursor by means of Prins reaction
and MacMillan aminoxylation sequence.
Received 27 June 2012
Revised 6 August 2012
Accepted 8 August 2012
Available online 14 August 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Prins cyclization
McMillan aminoxylation
2,4,5-Triols
Ring closing metathesis
OH
OH
2,4,5-Triols are important building blocks and found in many
biologically active molecules such as seimatopolide A, (2S,3R,5S)-
(ꢀ)-2,3-dihydroxy-tetradecan-5-olide, achaetolide, decarestrictine
O, galantinic acid, synparvolide B and botryolide E (Fig. 1). Many
polyketide natural products have been isolated from fungal sources
and are known to possess potent biological properties.1
Natural products with medium size lactone ring possess a wide
range of biological activities such as antibacterial and antifungal
behaviour.2 The seimatopolides constitute an 18-carbon polyhydr-
oxylated 10-membered lactone with E-configured double bond at
C-4. They were isolated from the extract of Seimatosporium disco-
sioides fungal culture medium.3 They are found to activate peroxi-
HO
OH
HO
OH
HO
O
O
O
O
( )5
( )7
OH
Achaetolide
1
OH
OAc OH
OH
OH
O
O
O
O
( )7
O
O
2
Botryolide E
Decarestrictine O
OAc
OH OH
O
some proliferator-activated receptor
c (PPAR-c) with EC50 values
H2N
OH
( )2
of 1.15 M. The structure of seimatopolides A (1) was proposed
l
OAc OH
Synparvolide B
O
OH
NH2
based on spectroscopic and modified Mosher’s method.
Toshima et al. have recently isolated the biologically active d-
lactone (2S,3R,5S)-(ꢀ)-2,3-dihydroxy-tetradecan-5-olide (2) from
Seridium unicome.4 It exhibits antifungal activity against Cladospo-
rium herbarum. Owing to the occurrence of 2,4,5-triols in various
polyketides, we were interested to develop a concise and practical
approach for the synthesis of 2,4,5-triol core structure.
O
Galantinic Acid
Figure 1. Examples of 2,4,5-triol containing natural products.
reductive cleavage and
a-aminoxylation sequence. Application of
such a chiral building block in natural product synthesis is then
exemplified through the total synthesis of seimatopolide A and
(2S,3R,5S)-(ꢀ)-2,3-dihydroxytetradecan-5-olide.
In this article, we wish to report a novel strategy for the synthe-
sis of 2,4,5-triol moiety by means of Prins cyclization followed by
In our retrosynthetic analysis (Scheme 1), we envisaged that the
target molecules 1 and 2 could be prepared from a common inter-
mediate 9, which was proposed to be obtained from the MacMillan
⇑
Corresponding author. Fax: +91 40 27160512.
E-mail address: basireddy@iict.res.in (B.V.S. Reddy).
a
-hydroxylation. The 2,4,6-trisubstituted tetrahydropyran core 5
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.08.027

5750
B. P. Reddy et al. / Tetrahedron Letters 53 (2012) 5749–5752
alcohol with 30 mol % CuSO4ꢁ5H2O gave chiral diol 9 in 60% overall
OH
yield (Scheme 2).7
HO
OH
Treatment of diol 9 with TsCl in the presence of TEA gave the
monotosylate which was then treated with K2CO3 in MeOH to fur-
nish epoxide 10 in 85% yield. Ring opening of epoxide 10 with
trimethylsulfonium iodide in the presence of n-BuLi in THF at
ꢀ20 °C gave the allylic alcohol in 88% yield8 which on further treat-
ment with MOMCl in the presence of Hunig’s base afforded MOM
ether 12 in 92% yield. Desilylation of compound 11 with TBAF re-
sulted in the formation of alcohol 12 in 89% yield. Next, we at-
tempted the coupling of alcohol 12 with a carboxylic acid 219 so
as to construct a 10-membered ring via RCM reaction. Under Steg-
lich conditions (DCC and DMAP), the coupling of alcohol 12 with an
acid 21 gave the corresponding ester 13 in 85% yield.10 Ring-clos-
ing metathesis reaction of 16 using Grubbs’ second generation cat-
alyst in CH2Cl2 at reflux temperature for 6 h gave compound 14 in
70% yield as a E-isomer.11 Deprotection of MOM ethers with 2 N
HCl gave the target molecule, seimatopolide A (1) in 88% yield
(Scheme 3). The spectral data (1H and 13C NMR) of seimatopolide
A (1) were identical to the data reported in the literature.12
After successful completion of seimatopolide A (1), we at-
tempted the synthesis of (2S,3R,5S)-(ꢀ)-2,3- dihydroxytetradecan-
5-olide using a common intermediate 9. Accordingly, monosilyla-
tion of diol 9 with TBSCl in the presence of imidazole gave the
TBDMS ether in 97% yield. Protection of secondary alcohol with
MOMCl in the presence of Hunig’s base afforded MOM ether 15.
Desilylation of compound 15 with TBAF resulted in the formation
of diol 16 in 83% yield. Chemoselective oxidation of 1,5-diol 16 with
TEMPO/BAIB system gave d-lactone 17 in 85% yield.13 Deprotection
of MOM group with aqueous hydrochloric acid in methanol afforded
the target molecule (2) in 87% yield (Scheme 4). The analytical data
of the target molecule were in good agreement with the data re-
ported in literature.12
O
TBS
O
OMOM
O
( )7
OH
( )7
1
OH
9
OH
OH
OH
OH
( )7
O
2
O
HO
OH
( )7
O
4
5
Scheme 1. Retrosynthetic analysis of seimatopolide
dihydroxy-tetradecan-5-olide.
A
and (2S,3R,5S)-(ꢀ)-2,3-
could be obtained via the Prins cyclization between homoallylic
alcohol 4 and n-decanal 3. We envisioned that polyhydroxy com-
pound (9) would be a common chiral synthon for accessing seima-
topolide A (1) and (2S,3R,5S)-(ꢀ)-2,3-dihydroxytetradecan-5-olide
(2) via the RCM and TEMPO/BAIB cyclization respectively.
Our strategy for the synthesis of seimatopolide A (1) is depicted
in Scheme 2. We began the synthesis of 1 with a homoallylic alco-
hol 4 which was prepared from (S)-benzyl glycidyl ether. Accord-
ingly, treatment of n-decanal 3 with a homoallylic alcohol 4
under Prins cyclization conditions afforded the 2,4,6-cis-trisubsti-
tuted tetrahydropyranol 5 in 73% yield with high diastereoselectiv-
ity.5 Chemoselective tosylation of primary alcohol 5 with 1.1 equiv
of tosyl chloride in the presence of TEA in DCM gave the corre-
sponding tosylate in 92% yield. Protection of secondary alcohol
with MOMCl in the presence of Hunig’s base afforded the MOM
ether 6 in 90% yield. Treatment of tosylate 6 with NaI in refluxing
acetone afforded the iodo compound in 94% yield, which upon
treatment with activated zinc in refluxing ethanol gave anti-1,3-
diol 7 in 90% yield.6 Protection of compound 7 with TBSCl and
imidazole afforded the corresponding TBS ether 8 in 97% yield.
Treatment of compound 8 with OsO4, 2,6-lutidine and NaIO4 gave
In summary, we have developed a concise approach to the total
synthesis of seimatopolide A and (2S,3R,5S)-(ꢀ)-2,3-dihydroxyte-
tradecan-5-olide using a common polyketide precursor 2,4,5-triol
unit. This approach successfully utilizes Prins cyclization, reductive
cleavage, and
a-aminoxylation synthetic sequence to the total
the corresponding aldehyde. Subsequent
a-amino-oxylation of
aldehyde with nitrosobenzene in the presence of D-proline in
DMSO at ꢀ10 °C, followed by treatment with NaBH4 in MeOH gave
the crude
a
-aminooxy alcohol. Further treatment of
a-aminooxy
OMOM
OH
O
TBS
O
OMOM
O
TBS
a
b
( )7
OH
( )7
9
10
OH
O
OMOM
TBS
OH OMOM
( )7
H
c
a
( )7
+
OH
OH
( )7
O
( )7
O
5
OMOM
HO
OMOM
12
11
4
3
OMOM
e
OMOM
d
MOMO
OMOM
OH
( )7
O
OMOM
O
b
c
OTs
( )7
HO
O
6
O
OMOM
21
OMOM
( )7
7
13
O
OMOM
TBS
MOMO
OMOM
OMOM
O
TBS
f
e
d
1
OH
( )7
O
( )7
OH
9
8
O
( )7
14
Scheme 2. Reagents and conditions: (a) TFA, CH2Cl2 then K2CO3, MeOH rt, 3 h, 73%;
(b) (i) TEA, TsCl, CH2Cl2, 0 °C to rt., 3 h, 92%; (ii) MOMCl, Hunig’s base, 0 °C to rt, 2 h,
90%; (c) (i) NaI, acetone reflux, 24 h, 94%; (ii) Zn, EtOH reflux, 1 h, 90%; (d) TBSCl,
imidazole, CH2Cl2 0 °C to rt., 3 h, 97%; (e) (i) OsO4, 2,6-lutidine, NaIO4, dioxane–H2O;
(ii) PhNO, D-proline (40 mol %), DMSO, rt, 30 min then NaBH4, EtOH, then CuSO4,
MeOH, 12 h.
Scheme 3. Reagents and conditions: (a) (i) TEA, TsCl, CH2Cl2, 0 °C to rt, 3 h, 92%; (ii)
K2CO3, MeOH; (b) (i) Me3SI, n-BuLi, THF, ꢀ20 °C, 88%; (ii) MOMCl, Hunig’s base, 0 °C
to rt, 2 h, 92%; (c) TBAF, THF, rt, 2 h, 83%; (d) DCC, DMAP, CH2Cl2, rt, 85%; (e) Grubbs
catalyst-II, CH2Cl2, reflux, 3 h, 70%; (f) 2 N HCl, THF, 15 h, rt, 87%.

B. P. Reddy et al. / Tetrahedron Letters 53 (2012) 5749–5752
5751
Reagents and conditions: (a) Me3SI, n-BuLi, THF, ꢀ20 °C, 88%; (b) (i) MOMCl,
Hunig’s base, 0 °C to rt, 2 h, 92%, (ii) Li-naphthalene, THF, ꢀ20 °C, 92%, (c) TEM-
OMOM
OH
OMOM
TBSO
( )7
TBSO
( )7
a
c
b
OH
OH
OTBS
OMOM
PO-BAIB, CH3CN, H2O (1:1) rt, 85%.
.
10. Murga, J.; Falomir, E.; Garcıa-Fortanet, J.; Carda, M.; Marco, J. A. Org. Lett. 2002,
4, 3447.
11. (a) Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28, 446; (b) Deiters,
A.; Martin, S. F. Chem. Rev. 2004, 104, 2199.
9
15
OMOM
OMOM
12. Spectral data for (2S,4R,6S)-2-(Hydroxymethyl)-6-nonyltetrahydro-2H-pyran-4-ol
(5): ½a 2D0
ꢂ
+12.5 (c 2.0, CHCl3); 1H NMR (300 MHz, CDCl3): d 3.90–3.74 (m, 1H),
OH OMOM
( )7
3.65–3.50 (m, 2H), 3.49–3.39 (m, 1H), 3.37–3.27 (m, 1H), 2.40 (br s, 2H), 1.95
(td, J = 12.0, 4.5, 2.2 Hz, 1H), 1.83 (td, J = 12.0, 4.5, 2.2 Hz, 1H), 1.61–1.50 (m,
1H), 1.48–1.36 (m, 1H), 1.33–1.07 (m, 16H), 0.96 (t, J = 6.8 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d 75.8, 75.7, 67.6, 65.5, 40.8, 36.7, 35.8, 31.7, 29.5, 29.4, 29.2,
25.4, 22.5, 13.9; IR (neat): mmax 2986, 2888, 1370, 1156, 1036 cmꢀ1; MS (ESI):
m/z 281 (M+Na)+, 258 (M+H)+.
d
2
( )7
O
O
OMOM
17
16
((2S,4R,6S)-4-(Methoxymethoxy)-6-nonyltetrahydro-2H-pyran-2-yl)methyl-4-
Scheme 4. Reagents and conditions: (a) (i) TBSCl, imidazole, CH2Cl2 0 °C to rt, 1 h,
97%; (ii) MOMCl, Hunig’s base, 0 °C to rt, 2 h, 92%; (b) TBAF, THF, rt, 2 h, 83%; (c)
TEMPO/BAIB, CH2Cl2, rt, 85%; (d) 2 N HCl, THF, 15 h, rt, 87%.
methylbenzenesulfonate (6): ½ ꢂ
a 2D0 +26.5 (c 2.0, CHCl3); 1H NMR (400 MHz,
CDCl3): d 7.78 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 8.3 Hz, 2H), 4.62 (s, 2H), 4.02–3.88
(m, 2H), 3.71–3.58 (m, 1H), 3.56–3.46 (m, 1H), 3.32 (s, 3H), 3.24 (m, 1H), 2.45
(s, 3H), 1.99–1.82 (m, 2H), 1.54–1.42 (m, 2H), 1.42–1.16 (m, 16H), 0.87 (t,
J = 6.2 Hz, 3H); 13C NMR (75 MHz, CDCl3): d 144.6, 132.0 129.6, 127.9, 94.3,
75.8, 72.7, 72.4, 72.0, 55.2, 38.1, 35.9, 35.8, 34.4, 31.8, 29.4, 29.2, 253, 22.6,
21.5, 14.0; IR (neat): mmax 2927, 2856, 1600, 1456, 1364, 1040, 981 cmꢀ1; MS
(ESI): m/z 479 (M+Na)+, 457 (M+H)+.
synthesis of seimatopolide A and (2S,3R,5S)-(ꢀ)-2,3-dihydroxyte-
tradecan-5-olide.
Acknowledgments
(4S,6S)-4-(Methoxymethoxy)pentadec-1-en-6-ol (7): ½a D20
ꢂ
+44.3 (c 2.0, CHCl3);
1H NMR (300 MHz, CDCl3): d 5.89–5.69 (m, 1H), 5.20–5.03 (m, 2H), 4.75–4.62
(m, 2H), 4.02–3.79 (m, 2H), 3.41 (s, 1H), 2.39–2.20 (m, 2H), 1.90 (br s, 1H),
1.68–1.52 (m, 1H), 1.46–1.35 (m, 1H), 1.35–1.12 (m, 18H), 0.90 (t, J = 6.0 Hz,
3H); 13C NMR (75 MHz, CDCl3): d 134.3, 117.4, 96.2, 75.2, 67.7, 55.7, 41.2, 39.4,
37.5, 31.8, 29.6, 29.5, 29.5, 29.2, 25.7, 22.6, 14.0; IR (neat): mmax 2986, 2888,
1370, 1156, 1036 cmꢀ1; MS (ESI): m/z 309 (M+Na)+.
B.P.R. and T.P.R. thank CSIR and UGC, New Delhi, for the award
of fellowships.
References and notes
(5S,7S)-5-Allyl-9,9,10,10-tetramethyl-7-nonyl-2,4,8-trioxa-9-silaundecane
(8):
½ ꢂ
a 2D0
+20.3 (c 2.0, CHCl3); 1H NMR (300 MHz, CDCl3): d 5.86–5.71 (m, 1H),
1. (a) Tarman, K.; Lindequist, U.; Wende, K.; Porzel, A.; Arnold, N.; Wessjohann, L.
A. Mar. Drugs 2011, 9, 294; (b) Maksimenka, H. K.; Reichert, M.; Perovic´-
Ottstadt, S.; Lin, W. H.; Wray, V.; Steube, K.; Schaumann, K.; Weber, H.; Proksch,
P.; Ebel, R.; Müller, W. E. G.; Bringmann, G. J. Nat. Prod. 2004, 67, 1532; (c)
Ratnayake, A. S.; Yoshida, W. Y.; Mooberry, S. L.; Hemscheidt, T. Org. Lett. 2001,
3, 3479; (d) Isaka, M.; Chinthanom, P.; Kongthong, S.; Supothina, S.;
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Intamas, S.; Kocharin, K.; Jones, E. B. G.; Kongsaeree, P.; Prabpai, S. Tetrahedron
2009, 65, 4396.
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365; (b) Collins, I. J. Chem. Soc., Perkin Trans. 1999, 1, 1377; (c) Grabley, S.;
Granzer, E.; Hutter, K.; Ludwig, D.; Mayer, M.; Thiericke, R.; Till, G.; Wink, J.;
Phillips, S.; Zeeck, A. J. Antibiot. 1992, 45, 56; (d) Gohrt, A.; Zeeck, A.; Hutter, K.;
Kirsch, R.; Kluge, H.; Thiericke, R. J. Antibiot. 1992, 45, 66; (e) Ayer, W. A.; Sun,
M.; Browne, L. M.; Brinen, L. S.; Clardy, J. J. Nat. Prod. 1992, 55, 649; (f) Niwa, H.
R.; Inagaki, H. A.; Yamada, K. Tetrahedron Lett. 1999, 32, 5127; (g) Congreve, M.
S.; Holmes, A. B.; Hughes, A. B.; Looney, M. G. J. Am. Chem. Soc. 1993, 115, 5815;
(h) Rivero-Cruz, J. F.; Garcia-Aguieee, G.; Cerda-Garcia-Rojas, C. M.; Mata, R.
Tetrahedron 2000, 56, 5337; (i) Tsuda, M.; Mugishima, T.; Komatsu, K.; Sone, T.;
Tanaka, M.; Mikami, Y.; Kobayashi, J. J. Nat. Prod. 2003, 66, 412.
5.11–4.98 (m, 2H), 4.63 (s, 2H), 3.85–3.75 (m, 1H), 3.73–3.63 (m, 1H), 3.35 (s,
3H), 2.30 (dt, J = 6.8, 5.3 Hz, 2H), 1.60–1.47 (m, 1H), 1.36–1.22 (m, 17H), 0.92–
0.86 (m, 12H), 0.05 (s, 6H); 13C NMR (75 MHz, CDCl3): d 134.6, 117.0, 95.9, 75.2,
69.6, 55.4, 42.3, 39.8, 38.0, 31.8, 29.8, 29.6, 29.5, 29.3, 25.9, 24.7, 22.6, 18.0,
14.0, -3.9, -4.4; IR (neat): mmax 2929, 2857, 1637, 1465, 1253, 1043 cmꢀ1; MS
(ESI): m/z 423 (M+Na)+.
(2R,3R,5S)-5-(tert-Butyldimethylsilyloxy)-3(methoxymethoxy)tetradecane-1,2-
diol (9): ½a 2D0
ꢂ
+10.3 (c 2.0, CHCl3); 1H NMR (300 MHz, CDCl3): d 4.74–4.61 (m,
2H), 3.87–3.75 (m, 1H), 3.70–3.54 (m, 4H), 3.42 (s, 3H), 2.40 (br s, 1H), 1.52–
1.40 (m, 1H), 1.34–1.15 (m, 7H), 0.91–0.83 (m, 12H), 0.06 (s, 3H), 0.05 (s, 3H);
13C NMR (75 MHz, CDCl3): d 97.4, 80.4, 73.9, 69.5, 63.6, 55.8, 38.9, 38.6, 37.9,
31.9, 29.7, 29.5, 29.5, 29.2, 25.8, 24.7, 24.6, ꢀ3.8, ꢀ4.4.; IR (neat): mmax 2986,
2888, 1370, 1156, 1036 cmꢀ1; MS (ESI): m/z 443 (M+Na)+, 421 (M+H)+.
(5R,6R,8S)-6-(Methoxymethoxy)-10,10,11,11-tetramethyl-8-nonyl-5-vinyl-2,4,9-
trioxa-10-siladodecane (11): ½a D20
ꢂ
+3.33 (c 2.0, CHCl3); 1H NMR (300 MHz,
CDCl3): d 5.87–5.74 (m, 1H), 5.35–5.28 (m, 2H), 4.78–4.59 (m, 4H), 4.22–4.09
(m, 1H), 3.90–3.74 (m, 2H), 3.39 (s, 3H), 3.38 (s, 3H), 1.50–1.21 (m, 20H), 0.89
(s, 12H), 0.07 (s, 3H), 0.06 (s, 3H); 13C NMR (75 MHz, CDCl3): d 134.8, 118.6,
97.4, 94.1, 79.0, 78.1, 69.5, 55.7, 55.6, 38.6, 38.2, 31.9, 29.8, 29.6, 29.5, 29.3,
25.9, 24,7, 22.6, 18.0, 14.1, ꢀ3.9, ꢀ4.5.; IR (neat):
mmax 2928, 2956, 1465, 1374,
1252, 1153, 1037 cmꢀ1 ; MS (ESI): m/z 433 (M+Na)+.
3. Hiep, N. T.; Choi, Y. H.; Kim, N.; Hong, S. S.; Hong, S. B.; Hwang, B. Y.; Lee, H. J.;
Lee, S. J.; Jang, D. S.; Lee, D. J. Nat. Prod. 2012, 75, 784.
(3R,4R,6S)-3,4-Bis(methoxymethoxy)pentadec-1-en-6-ol (12): ½a D26
ꢀ11.5 (c 2,
ꢂ
CHCl3); 1H NMR (300 MHz, CDCl3): d 5.75–5.67 (m, 1H), 5.34–5.27 (m, 2H),
4.84 (d, J = 6.3 Hz, 1H), 4.70 (dd, J = 3.1, 6.3 Hz, 2H), 4.58 (d, J = 6.3 Hz, 1H), 4.08
(t, J = 6.3 Hz, 1H), 3.86–3.78 (m, 2H), 3.43 (s, 3H), 3.38 (s, 3H), 2.98 (br s, 1H),
1.65–1.48 (m, 4H), 1.39–1.25 (m, 14H), 0.88 (t, J = 7.3 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d 134.5, 119.2, 98.2, 93.9, 79.7, 78.0, 67.4, 56.1, 55.5, 38.7,
37.4, 31.8, 29.6, 29.3, 25.7, 22.6, 14.1; IR (neat): mmax 2926, 2949, 1463, 1362,
1259, 1153, 1037; MS (ESI): m/z 369 [M+Na]+.
4. (a) Toshima, H.; Watanabe, A.; Sato, H.; Ichihara, A. Tetrahedron Lett. 1998, 39,
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Harnett, J. J.; Mioskowski, C.; Martel, J. P.; Gall, T. L.; Shin, D. S.; Falck, J. R.
Tetrahedron Lett. 1994, 35, 5449.
((3R,4R,6S)-3,4-Bis(methoxymethoxy)pentadec-1-en-6-yl)3-
(methoxymethoxy)pent-4-enoate (13): ½ ꢂ
a 2D0 +6.3 (c 2.0, CHCl3); 1H NMR
(300 MHz, CDCl3): d 5.88–5.67 (m, 2H), 5.42–5.18 (m, 4H), 4.73–4.63 (m,
4H), 4.60 (t, J = 6.7 Hz, 2H), 4.53–4.44 (m, 1H), 4.18–4.12 (m, 1H), 3.71–3.10 (m,
1H), 3.42–3.33 (m, 9H), 2.70–2.61 (m, 1H), 2.55–2.46 (m, 1H), 1.72–1.52 (m,
6H), 1.34–1.14 (m, 12H), 0.89 (t, J = 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3): d
170.2, 136.8, 134.3, 118.7, 118.1, 97.8, 94.3, 94.1, 78.7, 76.8, 73.8, 71.6, 56.0,
55.5, 41.0, 34.9, 31.8, 29.5, 29.2, 25.0, 22.6, 14.0; IR (neat): mmax 2927, 2856,
1734, 1458, 1371, 1152, 1034 cmꢀ1; MS (ESI): m/z 489 (M+H)+, 511 (M+Na)+.
(4R,7R,8R,10S,E)-4,7,8-Tris(methoxymethoxy)-10-nonyl-3,4,7,8,9,10-
9. Preparation of compound 21.
hexahydrooxecin-2-one (14): ½a D26
ꢂ
+26.8 (c 2, CHCl3); 1H NMR (300 MHz, CDCl3):
d 5.86–5.73 (m, 1H), 5.51 (dd, J = 10.0, 16.0 Hz, 1H), 4.85–4.56 (m, 6H), 4.55–
4.45 (m, 1H), 4.09 (dd, J = 4.0, 9.0 Hz, 1H), 3.94 (t, J = 9.0 Hz, 1H), 3.58–3.52 (m,
1H), 3.37 (s, 3H), 3.36 (s, 3H), 3.35 (s, 3H), 2.63 (dd, J = 3.0, 12.0 Hz, 1H), 2.51
(dd, J = 4.0, 12.0 Hz, 1H), 2.09–2.0 (m, 1H), 1.92–1.86 (m, 3H), 1.39–1.19 (m,
14H), 0.88 (t, J = 7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3): d 169.5, 134.8, 128.4,
97.6, 94.3, 93.7, 80.0, 75.1, 73.2, 70.2, 55.6, 55.4, 55.2, 41.8, 36.6, 31.8, 29.5,
29.3, 24.8, 22.6, 14.1; IR (neat): mmax 2939, 2851, 1735, 1465, 1379, 1156,
1043 cmꢀ1; MS (ESI): m/z 483 [M+Na]+.
OH
O
a
b
BnO
BnO
HO
19
18
O
OMOM
(5S,7R,8R)-7,8-Bis(methoxymethoxy)-2,2,3,3,11,11,12,12-octamethyl-5-nonyl-
OMOM
c
4,10-dioxa-3,11-disilatridecane (15): ½ ꢂ
a 2D0 +59.3 (c 2.0, CHCl3); 1H NMR
HO
(300 MHz, CDCl3): d 4.72–4.64 (m, 4H), 3.90–3.60 (m, 5H), 3.39 (s, 3H), 3.38
(s, 3H), 1.69–1.60 (m, 1H), 1.51–1.40 (m, 1H), 1.35–1.10 (m, 16H), 0.93–0.80
(m, 21H), 0.05 (s, 12H); 13C NMR (75 MHz, CDCl3): d 97.3, 97.0, 80.2, 75.5, 74.6,
21
20

5752
B. P. Reddy et al. / Tetrahedron Letters 53 (2012) 5749–5752
69.4, 62.4, 55.6, 38.6, 38.1, 31.8, 29.8, 29.6, 29.5, 29.2, 25.9, 25.8, 24.6, 22.6,
18.0, 14.0, -4.0, -4.4, -5.4, -5.5; IR (neat): mmax 2929, 1377, 1253, 1155, 1075,
2986, 2888, 1370, 1156, 1036 cmꢀ1; MS (ESI): m/z 369 (M+Na)+, 347 (M+H)+.
Seimatopolide A (1): ½a D20
ꢂ
ꢀ59.3 (c 2.0, MeOH); 1H NMR (500 MHz, pyridine-
916 cmꢀ1; MS (ESI): m/z 601 (M+Na)+, 579 (M+H)+.
d5): d 6.50 (dd, J = 9.9, 15.9 Hz, 1H), 6.19 (dd, J = 2.9, 15.9 Hz, 1H), 5.20 (dd,
J = 7.0, 13.0 Hz, 1H), 5.0 (bd, J = 2.0 Hz, 1H), 4.39 (t, J = 8.9 Hz, 1H), 3.99 (dd,
J = 7.9, 8.9 Hz, 1H), 2.90 (dd, J = 3.0, 11.0 Hz, 1H), 2.78 (dd, J = 4.0, 12.0 Hz, 1H),
2.36–2.26 (m, 2H), 1.8–1.60 (m, 2H), 1.39–1.22 (m, 14H), 0.92 (t, J = 7.0 Hz,
3H); 13C NMR (75 MHz, pyridine d5): d 170.2, 136.2, 128.0, 79.5, 76.9, 73.2,
67.2, 44.5, 42.0, 37.3, 32.0, 29.9, 29.7, 29.4, 25.4, 22.8, 14.2; IR (neat): mmax
3370, 2925, 2850, 2368, 1706, 1152, 1062 cmꢀ1; MS (ESI): m/z 351 (M+Na)+.
(2R,3R,5S)-2,3-Bis(methoxymethoxy)tetradecane-1,5-diol (16): ½a D20
ꢂ
+18.3 (c 2.0,
CHCl3); 1H NMR (300 MHz, CDCl3): d 4.81–4.67 (m, 4H), 4.02–3.92 (m, 1H),
3.83–3.70 (m, 2H), 3.70–3.61 (m, 2H), 3.44 (s, 6H), 3.03 (br s, 1H), 2.63 (br s,
1H), 1.73–1.62 (m, 3H), 1.49–1.38 (m, 1H), 1.35–1.14 (m, 14H), 0.87 (t,
J = 6.0 Hz, 3H); 13C NMR (75 MHz, CDCl3): d 97.8, 97.6, 83.0, 76.1, 67.7, 62.2,
56.0, 55.8, 38.3, 37.7, 31.8, 29.6, 29.5, 29.5, 29.2, 25.7, 22.6, 14.0; IR (neat): mmax
3437, 2926, 1462, 1212, 1149, 1034 cmꢀ1; MS (ESI): m/z 373 (M+Na)+.
(3S,4R,6S)-3,4-Dihydroxy-6-nonyltetrahydro-2H-pyran-2-one (2): ½ ꢂ ꢀ40 (c
a 2D0
(3S,4R,6S)-3,4-Bis(methoxymethoxy)-6-nonyltetrahydro-2H-pyran-2-one
(17):
2.0, CHCl3); 1H NMR (300 MHz, CDCl3): d 4.38–4.27 (m, 1H), 4.10–3.94 (m, 2H),
3.51 (br s, 1H), 2.90 (br s, 1H), 2.27 (td, J = 6.7, 3.0 Hz, 1H), 1.89–1.55 (m, 3H),
1.54–1.14 (m, 14H), 0.87 (t, J = 6.7 Hz, 3H); 13C NMR (75 MHz, CDCl3): d 78.5,
74.3, 69.0, 35.7, 35.6, 31.8, 29.4, 29.4, 29.2, 24.7, 22.6, 14.0; IR (neat): mmax
2986, 2888, 1370, 1156, 1036 cmꢀ1; MS (ESI): m/z 281 (M+Na)+, 259 (M+H)+.
13. Hansen, T. M.; Florence, G. J.; Mas, P. L.; Chen, J.; Abrams, J. N.; Forsyth, C. J.
Tetrahedron Lett. 2003, 44, 57.
½ ꢂ
a 2D0
+29.3 (c 2.0, CHCl3); 1H NMR (300 MHz, CDCl3): d 5.06 (d, J = 6.7 Hz,
1H), 4.82–4.69 (m, 3H), 4.34–4.23 (m, 1H), 4.15 (d, J = 8.3 Hz, 1H), 4.05–3.94
(m, 1H), 3.46 (s, 3H), 3.41 (s, 3H), 2.33 (qd, J = 7.5, 5.2, 4.5, 1.5 Hz, 1H), 2.02 (dt,
J = 7.5, 5.2, 1.5 Hz, 1H), 1.82–1.53 (m, 2H), 1.43–1.12 (m, 14H), 0.89 (t,
J = 6.0 Hz, 3H); 13C NMR (75 MHz, CDCl3): d 96.9, 96.0, 76.6, 75.2, 73.9, 56.1,
55.5, 35.5, 35.3, 31.8, 29.4, 29.4, 29.3, 29.2, 24.7, 22.6, 14.0; IR (neat): mmax